effects of irreversible acetylcholinesterase inhibition by isopropyl methylphosphonofluoridate on...
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Our results indicate that IMPF intoxication can produce changesin selected cytokines and immunoglobulins levels that may lead toimmune response disturbances.
doi:10.1016/j.toxlet.2010.03.678
200 Abstracts / Toxicology L
205-025pomoea carnea, a poisonous plant, promotes changes inymphocyte distribution of young rats
. Pípole 1, A.O. Latorre 1, I.M. Hueza 2
School of Veterinary Medicine and Animal Science, University Ofão Paulo, Brazil, 2 School of Pharmacy and Biochemistry, Federalniversity of São Paulo, Brazil
pomoea carnea (IC) is a poisonous plant found throughout Brazilnd other tropical countries. Natural toxicosis occurs when differ-nt farm animal species chronically ingest the plant. The main toxicompound of this plant is the swainsonine (SW), an indolizidinelkaloid that causes vacuolar lysosomal accumulation of incom-letely processed oligosaccharides. Alterations in the processf protein mannose glycosylation resulting in abnormal macro-olecules synthesis, leading to cellular adhesion and membrane
eceptors compromising and dysfunction of different system, asndocrine, digestive and immune. Despite of many studies of SWffect on immune system, this work is the first to evaluate the pos-ible toxic effect of IC on rats lymphocyte distribution; thus, fortyale Wistar rats aged about 21 days were divided into three exper-
mental groups which received daily, by gavage, during 14 days, 1,and 7 g/kg of IC aqueous extract (IC1, IC3 and IC7) and one con-
rol group (Co). Animal from Co-group received just water by theame way and period. On 15th experimental day, all animals wereilled and lymphocyte cells were collected from blood, spleen andhymus to determine cell phenotype employing flow cytometry.esults obtained from IC-groups showed an enhancement on thy-us CD8 cellularity; reduction on spleen CD8 and B cells and a
iminished number of CD4, CD8 and B cells on circulating blood.It is well known that lymphocytes express different cell
eceptors in order to perform proper migration in response tohemokines released by lymphoid organs; and it is also knownhat many chemokines and its receptors carry, in a step of theirynthesis, N-glycosylations of high mannose or hybrid type; thust is possible to assume that SW contained into IC aqueous extractould be implicated in abnormal lymphocyte circulation. Futuretudies will be conducted to better understand the effect of SW onymphocyte circulation.
oi:10.1016/j.toxlet.2010.03.676
205-026nfluences of inorganic lead (Pb) on anxiety-like behavior andtress responses in mice
. Kim
Korean Air Force Academy, Republic of Korea
ocomotive activity in a novel environment is an innate individualrait in humans and animals. Differential anxiety-like behavior isssociated with differential serum corticosterone (CORT) levels intressed mice. Pb is related to the fluctuation of serum CORT levelso a biological stress by bacterial infection and increased host-usceptibility to bacterial infection in mice. The specific aims of thistudy are to investigate influences of Pb on inter-individual differ-nces in their anxiety-like behavior and stress responses in mice.ocomotive activity for during the first 2 h in circular cage was ana-
yzed as an anxiety-like behavior. Higher anxiety-like behavior wasositively associated with higher serum CORT levels in the earlyime after bacterial infection. Mice with higher serum CORT lev-ls in early time after infection were more resistant to the bacterial196S (2010) S37–S351
infection than mice with lower serum CORT (p < 0.001). Pb-exposedmice have lower basal serum CORT levels than control mice(p < 0.05). Down-regulation of the hypothalamic–pituitary–adrenalaxis in Pb-exposed mice was associated with lower host-resistanceto bacterial infection. Pb disturbed an anxiety-like behavior innovel environment and adaption in repeated exposure to sameenvironment. Locomotive activity in repeated exposure to sameenvironment of Pb-exposed mice was significantly lower than con-trol mice (p < 0.001). Conclusively, an anxiety-like behavior of micein a novel environment may be indicative of an early induction of aCORT mediated stress response, which may contribute to improvedclearance of the bacteria or induction of immunity against low-dose infection. But the early induction of stress response by severestressor may turn rapidly on anti-inflammatory response, whichmay exacerbate the disease state. Pb exposure may delay theinduction of stress response and disturb anxiety-like behavior andadaptation in novel environments, and those may be related to dis-order of proper induction of inflammatory and anti-inflammatoryresponses after bacterial infection.
doi:10.1016/j.toxlet.2010.03.677
P205-027Effects of irreversible acetylcholinesterase inhibition byisopropyl methylphosphonofluoridate on Th1/Th2 response
R. Zdanowski, M. Paluch, J. Bany, M. Kowalczyk
Military Institute of Hygiene & Epidemiology, Poland
The main mechanism of toxic interaction of organophosphate com-pounds, including isopropyl methylphosphonofluoridate (IMPF),is the irreversible inhibition of acetylcholinesterase (AChE) activ-ity. This compound by blocking the enzyme, may affect thelevel of acetylcholine (cholinergic neuromediator), causing changesin the physiology of various cells (e.g. neurons, lymphocytes,macrophages, mast cells, etc.). Moreover, acetylcholine modulatessuch functions like proliferation, activation or inhibition of manyimmune cells and finally release of various cytokines.
The aim of this study was to examine the influence of IMPFadministration on the secretion of selected cytokines (IL-2, IL-4, IL-5, IFNg) and immunoglobulins (IgA, IgE) and check it out on thisbasis, the direction of the immune response. Experiments werecarried out on BALB/c male mice. Selected parameters were anal-ysed in serum samples collected at 1, 7, 14 and 21 days after IMPFintoxication (s.c., 100 �g/kg b.w.).
The studies showed changes in the secretion of two factors: IL-4and IL-5 (compared to control groups). In both cases, the statis-tically significant differences (increase of IL-4 and IL-5 decrease)were observed in 7 days after the IMPF poisoning. Similar to that,after 24 h and 7 days the level of IgE (versus control group) wassignificantly higher.